Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide

Abstract

A protometabolic approach to the origins of life assumes that the conserved biochemistry of metabolism has direct continuity with prebiotic chemistry. One of the most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for the synthesis of many other essential biomolecules. Aspartate’s prebiotic synthesis is complicated by the instability of its precursor, oxaloacetate. In this paper, we show that the use of the biologically relevant cofactor pyridoxamine, supported by metal ion catalysis, is sufficiently fast to offset oxaloacetate’s degradation. Cu2+-catalysed transamination of oxaloacetate by pyridoxamine achieves around a 5% yield within 1 h, and can operate across a broad range of pH, temperature, and pressure. In addition, the synthesis of the downstream product β-alanine may also take place in the same reaction system at very low yields, directly mimicking an archaeal synthesis route. Amino group transfer supported by pyridoxal is shown to take place from aspartate to alanine, but the reverse reaction (alanine to aspartate) shows a poor yield. Overall, our results show that the nodal metabolite aspartate and related amino acids can indeed be synthesised via protometabolic pathways that foreshadow modern metabolism in the presence of the simple cofactor pyridoxamine and metal ions.

Self-generating autocatalytic networks: structural results, algorithms and their relevance to early biochemistry

“…It has been known that pyruvate can lead to alanine in different experimental conditions [ 36 ], which this result hints at. Similarly, the minRAF obtained for l -aspartate points to the known short route to this amino acid via oxaloacetate [ 48 ]. Finally, it is interesting and consistent to observe that l -tryptophan and l -tyrosine have the largest minRAFs (21 and 28 reactions, respectively), as these aromatic amino acids are more complex and thought to appear later in prebiotic evolution.…”

Aspartate aminotransferase of Rhizobium leguminosarum has extended substrate specificity and metabolizes aspartate to enable N2 fixation in pea nodules

“…The resulting product, glutamate, acts as a universal amino group donor for various transamination reactions involved in the biosynthesis of other amino acids. A second important amino group donor is aspartate [ 1 ], which is involved in the biosynthesis of asparagine, threonine, arginine, methionine, lysine, purines, pyrimidines and other metabolites. Aspartate can be synthesized by transamination of the TCA cycle intermediate oxaloacetate from glutamate, forming α-ketoglutarate in the process.…”

Serpentinization as the source of energy, electrons, organics, catalysts, nutrients and pH gradients for the origin of LUCA and life

“…Subsurface reduction models have good congruence with microbial carbon and energy metabolism. Nucleic acid synthesis that might underpin an RNA world is more challenging under hydrothermal vent conditions ( Muchowska et al, 2020 ; Yi et al, 2022 ; Harrison et al, 2023 ) but at the same time, there is no clear evidence that an RNA world ever existed ( Baross and Martin, 2015 ) and there are no self-replicating RNA molecules in any life form as far as we know. Here we will focus on subsurface reduction as it occurs in modern serpentinizing systems as a starting point for origins.…”